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Steroid resistance in asthma

P J Barnes1, I M Adcock

  • 1Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.

QJM : Monthly Journal of the Association of Physicians
|July 1, 1995
PubMed
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Glucocorticoid resistance in asthma is uncommon but challenging. It stems from altered glucocorticoid receptor (GR) binding to DNA, often due to interactions with transcription factors like AP-1.

Area of Science:

  • Immunology
  • Pharmacology
  • Respiratory Medicine

Background:

  • Glucocorticoid therapy is a cornerstone for inflammatory diseases like asthma.
  • Steroid resistance, though uncommon, poses significant clinical management challenges.
  • Understanding steroid resistance mechanisms offers insights into steroid action and disease pathology.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying primary and secondary steroid resistance in asthma.
  • To explore the role of transcription factors in glucocorticoid receptor (GR) function.
  • To identify potential therapeutic strategies for steroid-resistant asthma.

Main Methods:

  • Investigated pharmacokinetic profiles and GR binding in primary steroid-resistant (SR) asthma.

Related Experiment Videos

  • Assessed GR binding to DNA and interactions with transcription factors, including activator protein-1 (AP-1).
  • Examined the impact of cytokines and beta 2-agonists on GR function in secondary steroid resistance.

    • Main Results:

    • Primary SR asthma shows normal steroid pharmacokinetics and GR binding to the receptor.
    • A key finding is reduced GR binding to DNA, linked to increased GR binding to AP-1.
    • Secondary resistance involves cytokines and beta 2-agonists activating transcription factors that interfere with GR.

    Conclusions:

    • Steroid resistance in asthma is primarily mediated by altered GR-DNA binding, not receptor defects.
    • Interactions between GR and transcription factors like AP-1 and CREB are critical in resistance.
    • Novel and existing treatment strategies can be developed for managing SR asthma.